Nanotechnology delivers hepatitis B vaccine

July 11, 2019

Brazilian and European researchers have demonstrated exactly how a nanotechnology-based compound delivers an oral vaccine against hepatitis B to the immune system. When particles containing silica and an antigen combine, even though they are different sizes, they reach the intestine without being destroyed by the acidity of the digestive system.

A compound of nanostructured SBA-15 silica and HBsAg, the hepatitis B surface antigen, was submitted to different types of X-ray imaging in European laboratories.

The nanostructured silica was developed by researchers at the University of São Paulo's Physics Institute (IF-USP) in Brazil. The antigen was created by the Butantan Institute, which is also in São Paulo.

The study was supported by São Paulo Research Foundation - FAPESP and European research funders. The results are published in Scientific Reports.

The aim of the study was to understand how 22 nanometers-sized antigen binds to silica nanotubes with a diameter of approximately 10 nanometers and a honeycomb-like structure. One nanometer (1 nm) is a billionth of a meter.

Studies carried out at USP revealed the measurements of both the antigen and the silica nanotubes using small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and transmission electron microscope.

"Despite the size difference, tests [in animals] produced an excellent immune response to the oral vaccine - as good as the injectable form or better," said Márcia Fantini, Full Professor at IF-USP.

X-ray and neutron imaging was coordinated by Heloisa Bordalo, a Brazilian researcher at the University of Copenhagen's Niels Bohr Institute in Denmark. In collaboration with other researchers in Denmark as well as colleagues in France, Germany, Sweden and Switzerland, Bordalo submitted the compound to small-angle X-ray scattering (SAXS), among other techniques.

The three-dimensional images obtained by these techniques showed that although the antigen did not enter the nanotubes, it was retained in 50 nm macropores between the nanotubes. This protected it from the acidity of the digestive system.

The images also enabled the researchers to determine the ideal proportion of silica and HBsAg so that the antigen did not agglomerate, hindering the dispersion of the active principle in the patient's intestine.

"The oral and intranasal routes are natural modes of vaccine administration. Nature is the best vaccination agent. However, a vaccine that contains a protein, as in this case, is destroyed by high acidity and its own proteases in passing through the stomach, so it doesn't reach the immune system, particularly the small intestine," said Osvaldo Augusto Sant'Anna, Scientific Leader at Butantan Institute and responsible for development of the HbsAg antigen.

Before proceeding to clinical trials, the team will test polymers that can be used to coat the entire structure and increase the medication's resistance to the human stomach. In animal trials, the formulation proved to be as effective as the injected vaccine, if not more so, in delivering the antigen to the intestine, where the immune system can detect it and produce antibodies against the virus.

According to the World Health Organization (WHO), approximately 257 million people currently live with hepatitis B worldwide.

Polyvaccine

Through a project supported by FAPESP, the group led by Sant'Anna, Fantini and Bordalo is now developing new antigens to add to the compound. The idea is to have at least a triple vaccine by adding other antigens against diphtheria and tetanus.

However, the formulation may evolve to become a polyvaccine that also immunizes people against whooping cough, poliomyelitis and Haemophilus influenzae type B (Hib), the bacterium that causes meningitis and pneumonia, among other diseases.

The antigens must combat the diseases without interfering with each other. "There have been very interesting results with diphtheria, and we're now going to test it for tetanus, initially in injectable form," Sant'Anna said.
-end-
About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at http://www.fapesp.br/en and visit FAPESP news agency at http://www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.

Fundação de Amparo à Pesquisa do Estado de São Paulo

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.